Identification of genes associated with multiple nodules in hepatocellular carcinoma using cDNA microarray: multicentric occurrence or intrahepatic metastasis?
Identification of genes associated with multiple nodules in hepatocellular carcinoma using cDNA microarray: multicentric occurrence or intrahepatic metastasis?
复制标题
DOI：
--
复制
发表时间：
2008-05
影响因子：
--
通讯作者：
Takenari Nakata;N. Seki;Shire Miwa;A. Kobayashi;J. Soeda;Y. Nimura;S. Kawasaki;S. Miyagawa
中科院分区：
文献类型：
--
作者：
Takenari Nakata;N. Seki;Shire Miwa;A. Kobayashi;J. Soeda;Y. Nimura;S. Kawasaki;S. Miyagawa
背景/目的肝细胞癌因肝内转移(IM)或多中心癌变(MC)多发，预后不良。这项研究比较了微阵列分析在诊断这两种类型中的有效性与常规组织病理学诊断的有效性。其目的是通过描绘多结节肝癌的克隆性来识别IM或MC相关基因。方法应用由4,608个基因组成的基因芯片进行全基因组表达谱分析，从11个手术切除的肝脏标本中获得23个肿瘤灶的克隆关系。结果原发性肝细胞癌IM的基因表达特征与其相应的IM非常相似，提示促进转移的基因在原发灶中启动。相比之下，在多中心性肝癌中观察到不同的基因表达。实时定量聚合酶链式反应和免疫组织化学证实，肾上腺髓质素基因已被确定为基因表达特征中的先导基因，在肝细胞癌中过表达。结论基因芯片表达谱分析为揭示肝癌多发结节的克隆关系和寻找转移相关基因提供了可靠的方法。肾上腺髓质素是与人肝细胞癌IM进展相关的一个因素。
BACKGROUND/AIMS The prognosis of hepatocellular carcinoma (HCC) is poor because of frequent intrahepatic metastasis (IM) or multicentric carcinogenesis (MC). This study compared the effectiveness of microarray analysis in the diagnosis of these 2 forms with that of conventional histopathological diagnosis. The aim was to identify IM- or MC-associated genes through delineation of the clonality of multinodular liver cancer. METHODOLOGY The clonal relationship of 23 tumor foci obtained from 11 surgically resected liver specimens was investigated by genome-wide expression profiling via an in-house cDNA microarray consisting of 4,608 genes. RESULTS The gene expression signature of primary HCCs with IM was very similar to that of their corresponding IMs, implying that genes favoring progression of metastasis were initiated in the primary tumors. In comparison, different gene expression was observed in multicentric HCCs. The gene for adrenomedullin, which has been identified as a lead gene in the gene expression signature, was overexpressed in HCCs with IM, as confirmed by real time-PCR and immunohistochemistry. CONCLUSIONS Analysis of expression profiles by microarray could provide a reliable method of delineating the clonal relationship of multiple nodules of liver cancer and identifying metastasis-associated genes. Adrenomedullin is a factor associated with progression of IM in human HCC.